|Year : 2014 | Volume
| Issue : 2 | Page : 365-367
Generalized vitiligo post radiotherapy in a breast cancer patient
Gangadhar Vajrala1, Piyush K Jain1, Shitalkumar Surana1, Donald J Fernandes2
1 Department of Radiation Oncology, Krishna Institute of Medical Sciences, Secunderabad, Andhra Pradesh, India
2 Department of Radiotherapy and Oncology, Kasturba Medical College, Manipal, Karnataka, India
|Date of Web Publication||14-Jul-2014|
11-3-148, Road No 13, S V Colony, Saroornagar, Hyderabad-500 035, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Vitiligo is a common depigmentation disorder of skin, etiology of which is poorly understood. It has been rarely reported as a consequence of radiation at the site of irradiation, more so in patients with prior history of vitiligo. We report a rare clinical vignette that documents radiation-induced skin depigmentation, which started at the irradiated site and later manifested as generalized vitiligo, in a breast cancer patient with no family history of vitiligo. Studies describing the relationship between skin depigmentation and radiotherapeutic dose are scanty. The possible etiopathological mechanisms of vitiligo and radiation as a potential triggering factor for its development, which has been described in the literature, have been highlighted in this article.
Keywords: Breast cancer, depigmentation, radiotherapy, vitiligo
|How to cite this article:|
Vajrala G, Jain PK, Surana S, Fernandes DJ. Generalized vitiligo post radiotherapy in a breast cancer patient. J Can Res Ther 2014;10:365-7
| > Introduction|| |
Vitiligo is an acquired cutaneous depigmentation disorder that occurs in approximately 0.5-1% of the population worldwide. , Vitiligo does not have predilection for age, gender or ethnic background and is probably multifactorial in origin - involving genetic, autoimmune, neurologic, and metabolic factors. Association of this depigmentation disorder with irradiation has rarely been reported in the literature. , We report a rare case of radiation induced, generalized depigmentation, in a breast cancer patient, who had no history of vitiligo [Figure 1]. We further discuss the possible etiopathological mechanisms of radiation induced, generalized vitiligo.
| > Case report|| |
A 60-year-old postmenopausal woman with no history of vitiligo presented with right-sided breast lump of four months duration. After relevant investigations patient was diagnosed with breast cancer and was subjected to lumpectomy and axillary dissection. Her post-operative histopathology report showed mixed carcinoma with infiltrating ductal and lobular components, grade 2, with a tumor of size 3.5 × 4 cm infiltrating 4 out of 16 lymph nodes and base. Lymphovascular emboli, peri-neural invasion or extensive intraductal components were not present. The hormone receptor status was positive; her-2-neu receptor status was negative (1+); Ki-67 and p53 were not done. The tumor was staged as pT2 N2 M0. Subsequently, the patient received 4 cycles of 3 weekly Doxorubicin (at 60 mg/m 2 ) and Cyclophosphamide (at 600 mg/m 2 ) followed by 4 cycles of 3 weekly Paclitaxel (at 175 mg/m 2 ) as adjuvant chemotherapy. Thereafter the patient received loco-regional radiotherapy on a linear accelerator machine to a total dose of 46 Gy in 23 fractions over a period of 34 days. Radiotherapy was delivered in five fields utilizing two tangential portals for the chest wall, anterior-posterior-posterio-anterior (AP-PA) fields for the axillary and supraclavicular regions and, one field for the internal mammary chain. Patient developed dry desquamation (grade 2 skin reaction) at approximately 3 weeks after the initiation of radiotherapy, and grade 3 skin reaction by the end of 5 th week, which subsided completely by the first follow-up visit. Later the patient was on hormone therapy and on regular follow-up. Nine months after the completion of radiotherapy patient complained of a whitish discoloration in her chest and was clinically detected to have a small de-pigmented patch with well-demarcated borders in the irradiated region, without any skin atrophy or subcutaneous fibrosis. Soon this depigmented patch spread to involve other side of the chest, face, hands, and feet [Figure 2],[Figure 3] and [Figure 4]. The patient was referred to dermatologist, where she was diagnosed to have extensive vitiligo vulgaris, also called as non-segmental vitiligo or generalized vitiligo. Complete blood picture, antithyroglobulin antibodies, thyroid function tests were conducted as per recommendations, which were all within normal limits. Since all the series of clinical events leading to generalized vitiligo started after completion of radiotherapy and the depigmentation started at the irradiated site in our patient who had no family history of vitiligo or any other known triggering agent, it was diagnosed as radiation-induced vitiligo, a diagnosis of exclusion.
| > Discussion|| |
Vitiligo is a common depigmentation disorder of skin, etiology of which is poorly understood. Vitiligo post-irradiation has often been reported in the earlier studies as a Koebner's phenomenon (KP), where newer lesions of the pre-existing skin disease develop following various kinds of trauma to the uninvolved skin.  Our patient did not have a history of vitiligo prior to radiation, akin to some previous studies.  Few cases of vitiligo post radiotherapy in cancer sites other than breast have also been reported in the past. ,
Development of vitiligo has been attributed to complex interaction of genetic, autoimmune, neurologic, and biochemical factors. The underlying mechanism of destruction of melanocytes in vitiligo has been described as apoptosis of susceptible melanocytes. ,,,, Free radicals generated by radiotherapy and oxidative stress in the irradiated cells have been shown to cause apoptosis of vitiliginous melanocytes in many studies. Generation of ceramide, a second messenger, by the effect of radiation on the plasma cell membrane has also been shown to activate apoptotic response through mitochondrial system. 
Among the studies reported previously, post radiotherapeutic depigmented patches were shown to be confined to the site of irradiation. ,, Very few studies reported radiation induced, generalized vitiligo. , The reported interval for appearance of vitiligo after completion of radiotherapy varies from 2 months (Munshi et al.) to 40 months (Pajonk et al.) in literature. , Our patient developed localized depigmented patches after 9 months of completion of radiotherapy, which eventually progressed to become generalized within a short course of time. The exact pathogenic mechanism of generalized spread of vitiligo is still unclear. Earlier conducted genome wide linkage studies identified several generalized vitiligo susceptibility genes that eventually control biological pathways involved in the immune regulation of melanocytes. , A "two-hit" mechanism has been proposed wherein localized radiotherapy leads to formation of neoantigens due to oxidative stress, which eventually induce a systemic immune response causing generalized vitiligo.  Some earlier studies have also indicated that imbalance in the oxidant-antioxidant systems caused by the free radical-mediated damage can act as an initial pathogenic event in generalized vitiligo. , The proposed mechanism for extensive depigmentation in our case is initiation of systemic autoimmune response due to free-radicals generated by radiotherapy along with genetic susceptibility.
The severity of radiation-induced skin injury, time interval and variations in expression of skin changes after radiotherapy have been extensively discussed and correlated with dose, fractionation, and size of irradiated skin.  However, limited studies describe a correlation between dose of radiation and vitiligo. One study showed that radiation-induced hypopigmentation appeared only in the skin irradiated with tangent portals and not in the area irradiated with supraclavicular portal, when treated up to a dose of 45Gy using telecobalt machine.  Another study showed complete depigmentation in the localized region that received 40Gy of external beam radiotherapy.  These studies suggest higher skin dose delivered with tangential beams might have led to localized depigmentation. Our patient received a total dose of 46Gy of irradiation but the depigmentation soon evolved to become generalized vitiligo. This gives an indication that development of radiation-induced vitiligo might depend upon other factors like genetic predisposition or systemic oxidative stress rather than local factors like radiotherapeutic dose alone.
| > Conclusion|| |
Our case report suggests the possibility of occurrence of vitiligo after irradiation in patients with no history of vitiligo. Another important aspect, which warrants further research, is the progression of radiation induced, localized vitiligo and manifestation of generalized vitiligo. Future studies that can increase the understanding of pathogenic mechanisms of vitiligo, specifically focusing on the relationship between depigmentation and radiotherapy, also might be helpful. Considering specific factors that predispose to development of vitiligo during the protocol planning and explaining the risks and benefits of radiotherapy to the patient in this context can avoid undesirable cosmetic outcomes of radiotherapy.
| > Acknowledgement|| |
Dr. TK. Krishna Sharan, Dr. P U. Saxena, Mr. Srinidhi Chandragutti.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]